Angioimmunoblastic T-cell lymphoma (AITL) is one form of peripheral T-cell lymphoma (PTCL), and a disease that accounts for about 20% of the entire T-cell lymphomas. AITL often presents autoimmune-disorder-like clinical symptoms such as generalized lymphadenopathy and polyclonal hypergammaglobulinemia. In terms of histology based on immunohistological staining, the structure of the lymph node is found to have increases in polymorphic tumor cells and inflammatory cells such as reactive lymphocytes and eosinophils and is associated with an increase in high endothelial venules and follicular dendritic cells. B-cell immunoblasts are also present in the lymph node, which are often EB-virus-positive. The tumor cells are usually CD4-, CD10-, PD1- or CXCL13-positive.
Focusing on gene expression, the fact that the majority of the T-cell lymphomas are associated with rearrangement of T-cell receptor (TCR) will help with diagnosis. However, such TCR rearrangement may not be detected in AITL. On the other hand, rearrangement of the immunoglobulin that is usually detected in B-cell lymphomas is found in 30% of the cases. Accordingly, distinguishing AITL from other lymphomas such as B-cell lymphomas may sometimes be difficult. Based on such results of immunohistological staining patterns and characteristic gene expression profiles, the normal counterpart of the AITL tumor cell is considered to be one form of helper T-cells called follicular helper T-cell (TFH).
Meanwhile, peripheral T-cell lymphomas not otherwise specified (PTCL-NOS) account for 30% of the T-cell lymphomas. This disease name is used for peripheral T-cell lymphomas that have no feature characteristic enough to be diagnosed as specific peripheral T-cell lymphomas, and represents more heterogeneous disease concept in that they lack features as an independent disease group. Some of PTCL-NOS express a TFH marker, and may have morphological characteristic of AITL. There is no certain opinion about whether such marginal cases should be diagnosed as AITL or PTCL-NOS. At this point, the diagnosis depends on the principle of individual pathologists.
As described above, AITL (or AITL-like PTCL-NOS) is often difficult to be distinguished from other lymphomas such as B-cell lymphomas or from reactive changes. Therefore, an objective diagnostic method for distinguishing these diseases has been required in clinical practice and clinical research.
As pathological conditions of AITL in terms of molecular biology, gene mutations in TET2, IDH2 and DNMT3A have recently been identified, and mutations in the same genes, although less frequently, have also been reported in the cases of PTCL-NOS. However, since all of these gene mutations are also observed in myeloid tumors, they do not seem to contribute to a pathological image that is characteristic of AITL. Thus, a gene mutation specific to AITL had not been reported.